Mononuclear phagocytes have important functions in the host's defenses against injury. Mononuclear phagocytes recognize and destroy neoplastic cells in vitro, when the macrophages are activated. However, the metabolic basis of activation, the way in which activated macrophages destroy neoplastic cells and the fundamental mechanisms regulating activation are ill-defined. The nonspecific cytotoxicity of activated macrophages and the secretion of neutral proteases by macrophages are linked. We therefore propose to: A) Determine the relationship between macrophage-mediated cytotoxicity and the secretion of neutral proteases; B) Determine if macrophages secrete a soluble cytotoxin and, if so determine its character and relationship to neutral proteases; C) Delineate the mechanisms regulating secretion of neutral proteases; and D) Delineate the the factors regulating the activation and cytotoxic expression of activated macrophages. The ultimate goals of these studies are to understand how the cytoxic function of macrophages is regulated and to apply this knowledge to models of chronic inflammation and tumor destruction in vivo.